title: Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma.
abstract: BACKGROUND
  The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC.
  
  
  METHODS
  Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis.
  
  
  RESULTS
  GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations.
  
  
  CONCLUSIONS
  Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial.
authors.affiliation: Department of Cancer and Inflammation Research, Institute for Molecular Medicine (IMM), University of Southern Denmark, Winsloewparken 25, 3, Odense C, DK-5000, Denmark. mgjerstorff@health.sdu.dk.
authors.forename: Morten F
authors.initials: MF
authors.lastname: Gjerstorff
authors.forename: Mette
authors.initials: M
authors.lastname: Pøhl
authors.forename: Karen E
authors.initials: KE
authors.lastname: Olsen
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Ditzel
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D013737:Testis / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; C090172:SPA17 protein, human